From the Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (O.M., C.W.M., Y.G., J.A.J.); Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); College of Pharmacy, University of Texas, Austin (R.L.T.); Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore (R.B.H., A.R.S., B.D.M.); Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.); and Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

From the Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (O.M., C.W.M., Y.G., J.A.J.); Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); College of Pharmacy, University of Texas, Austin (R.L.T.); Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore (R.B.H., A.R.S., B.D.M.); Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.); and Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

From the Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (O.M., C.W.M., Y.G., J.A.J.); Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); College of Pharmacy, University of Texas, Austin (R.L.T.); Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore (R.B.H., A.R.S., B.D.M.); Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.); and Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

From the Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (O.M., C.W.M., Y.G., J.A.J.); Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); College of Pharmacy, University of Texas, Austin (R.L.T.); Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore (R.B.H., A.R.S., B.D.M.); Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.); and Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

From the Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (O.M., C.W.M., Y.G., J.A.J.); Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); College of Pharmacy, University of Texas, Austin (R.L.T.); Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore (R.B.H., A.R.S., B.D.M.); Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.); and Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

From the Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (O.M., C.W.M., Y.G., J.A.J.); Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); College of Pharmacy, University of Texas, Austin (R.L.T.); Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore (R.B.H., A.R.S., B.D.M.); Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.); and Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

From the Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (O.M., C.W.M., Y.G., J.A.J.); Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); College of Pharmacy, University of Texas, Austin (R.L.T.); Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore (R.B.H., A.R.S., B.D.M.); Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.); and Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

From the Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (O.M., C.W.M., Y.G., J.A.J.); Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); College of Pharmacy, University of Texas, Austin (R.L.T.); Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore (R.B.H., A.R.S., B.D.M.); Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.); and Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

From the Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (O.M., C.W.M., Y.G., J.A.J.); Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); College of Pharmacy, University of Texas, Austin (R.L.T.); Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore (R.B.H., A.R.S., B.D.M.); Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.); and Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

From the Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (O.M., C.W.M., Y.G., J.A.J.); Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA (L.A.M.); College of Pharmacy, University of Texas, Austin (R.L.T.); Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore (R.B.H., A.R.S., B.D.M.); Department of Neurology, University of British Columbia, Vancouver, Canada (O.R.B.); and Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.).

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Abstract

Background and Purpose—Functional polymorphisms (Ser49Gly and Arg389Gly) in ADRB1 have been associated with cardiovascular and β-blocker response outcomes. Herein we examined associations of these polymorphisms with major adverse cardiovascular events (MACE), with and without stratification by β-blocker treatment in patients with a history of stroke.

Methods—Nine hundred and twenty-six participants of the SPS3 trial’s (Secondary Prevention of Small Subcortical Strokes) genetic substudy with hypertension were included. MACE included stroke, myocardial infarction, and all-cause death. Kaplan–Meier and multivariable Cox regression analyses were used. Because the primary component of MACE was ischemic stroke, we tested the association of Ser49Gly with ischemic stroke among 41 475 individuals of European and African ancestry in the NINDS (National Institute of Neurological Disorders and Stroke) SiGN (Stroke Genetics Network).

Conclusion—Among individuals with previous small artery ischemic stroke, the ADRB1 Gly49 polymorphism was associated with MACE, particularly small artery ischemic stroke, a risk that may be increased among β-blocker-treated individuals. Further research is needed to define β-blocker benefit among ischemic stroke patients by ADRB1 genotype.